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Dysregulated proline metabolism contributes to retinal fibrosis in neovascular AMD: Therapeutic potential of prolyl-4-hydroxylase inhibition

Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (AMD). This study shows that proline metabolism, particularly P4HA1-mediated proline hydroxylation, is activated in JR5558 mice and human AMD tissues. Diethyl pythiDC reduced collagen turnover and fibrovascular lesion expansion, with potential added benefit when combined with aflibercept.

KernelGenBench: Can LLMs and Agents Write Efficient Kernels Across Operator Sources and Hardware Platforms?

arXiv:2607.27231v3 Announce Type: replace Abstract: Modern AI systems depend on specialized accelerator kernels, whose development is complicated by increasingly diverse operators and hardware. LLMs and agentic systems promise to automate this work, but existing evaluations do not show whether their performance transfers across operator sources and hardware platforms, or what such transfer costs. We present KernelGenBench, the first unified multi-source and multi-chip infrastructure for evaluating LLM- and agent-generated Triton kernels. With a common Triton target spanning six hardware platforms, it provides the broadest cross-vendor hardware coverage among existing kernel-generation benchmarks. We report two controlled analytical views: KernelGenBench-MS (Multi-Source) covers 210 operators from PyTorch ATen, production vLLM operators, and proprietary cuBLAS routines, while KernelGenBench-MC (Multi-Chip) evaluates a semantically stable 110-operator subset across six hardware platforms. Our evaluation consumed over 15 billion tokens. Agentic execution improved correctness, but no method dominated across sources and platforms: vLLM posed the strongest correctness challenge, cuBLAS set the highest performance ceiling, and AutoKernel accuracy fell from 87% on NVIDIA to 25% on Iluvatar CoreX. These improvements were costly: specialized agents averaged 4.99 million tokens per successful operator, rising to 6.25 million for CUDA Optimized Skill. The results establish operator source, hardware platform, and agentic scaffold as distinct dimensions of kernel-generation capability, and show that success in a familiar source-hardware setting is not a reliable proxy for deployment readiness.

Local lactate-driven H3K18 lactylation impairs anti-influenza immunity through NRF2-dependent dendritic cell dysfunction

Cell Rep. 2026 Sep 3;45(9):117943. doi: 10.1016/j.celrep.2026.117943. Online ahead of print.

ABSTRACT

Metabolic alterations are increasingly recognized during influenza virus infection, but how local lactate accumulation shapes antiviral immunity remains poorly characterized. By integrating time-series targeted energy metabolomics, single-cell RNA sequencing, flow cytometry, and functional perturbation, we show that influenza virus infection preferentially increases lactate within the lung microenvironment, where it restrains pulmonary CD8+ T cell response. Mechanistically, extracellular lactate enters dendritic cells through monocarboxylate transporter (MCT)-dependent transport and induces a tolerogenic-like state marked by impaired maturation, reduced costimulation, and diminished CD8+ T cell-priming capacity. Direct experimental evidence identifies H3K18la as a prominent lactate-responsive histone lactylation mark, while multi-omics integration links it to enhancer accessibility and NRF2 pathway activation. Functional studies further show that NRF2 promotes dendritic cell suppression by reinforcing tolerogenic programs and limiting mtROS-dependent XBP1 splicing. Together, these findings reveal a lactate-driven histone lactylation-NRF2 pathway that modulates antiviral immunity during influenza infection.

PMID:42690934 | DOI:10.1016/j.celrep.2026.117943

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